We are particularly interested in attempting to measure the pharmacodynamic effects of antiepileptic drugs in vivo. Using positron emission tomography (PET) with 18-fluorodeoxyglucose and 150-water, we studied the effect of vigabatrin (VGB), an experimental antiepileptic drug that raises GABA levels by inhibiting GABA transaminase. Global CMRglc was significantly lower when patients were taking VGB (6.95 +/- 0.58 vs 7.78 +/-1.1; P<O.03), and significantly reduced on the second PET scan for VGB but not placebo patients. Mean reduction was 7+/-6%. CSF GABA was higher when patients were on VGB. There was a significant relation between the rise in CSF GABA and fall in CMRglc. The data will be analyzed with statistical parametric mapping to detect any regionally specific effects, that could be related to the presence of epileptic foci. We also measured the effect of VGB on brain GABA using magnetic resonance spectroscopy (MRS), in 8 patients with temporal lobe epilepsy taking vigabatrin, and 7 controls. Voxels were positioned in the medial posterior parietal region, distant from epileptic foci. Metabolite peaks in each spectra were processed on Sun Mlcrosystems SPARC stations with Spectroscopy Analysis General Electric software. Marker peaks (MPG) for 2- CH2 GABA and glutamine-glutamate resonance regions were measured. Mean MRS GABA peaks were higher in patients than controls. There was a significant relation between CSF and MRS GABA measurements. VGB's reduction in CMRglc is related to increased brain GABA levels. The low level of the effect is consistent with its mild impairment of cognitive function. Drugs which raise GABA levels may not affect these parameters as much as agents like PB, which have other important physiologic actions. In future pharmacodynamic studies, we will use EEG, neuropsychological testing, and transcranial magnetic stimulation to study the effects of experimental antiepileptic drugs on learning and memory, sleep, and intracortical excitability.